Prevention of long-term complications of
non-insulin-dependent diabetes mellitus
David M. Nathan
Harvard Medical School, Diabetes Clinic and
Diabetes Research Center, Massachusetts General
Hospital, Boston, Massachusetts, USA
Copyright 1996 Canadian Medical Association
Abstract
Non-insulin-dependent diabetes mellitus (NIDDM) may be the most
rapidly-growing chronic disease in the world. Its long-term
complications, including retinopathy, nephropathy, neuropathy, and
accelerated macrovascular disease cause major morbidity and
mortality. Although therapy that normalizes glycemia may prevent
the development and delay the progression of long-term
complications in NIDDM, as has been demonstrated in insulin-dependent
diabetes mellitus (IDDM), no direct data exist to support
the efficacy of "intensive therapy" in NIDDM. An alternative
approach to preventing the development of long-term
complications may be to intervene more distally, i.e., inhibit the
mechanism(s) by which elevated glucose levels cause complications.
Potential pathogenic mechanisms include the accumulation of
sorbitol and other biochemical changes in tissues with aldose
reductase, and the modfication of proteins by glycation.
Pharmacologic probes, including aldose reductase inhibitors and
glycation inhibitors such as aminoguanidine, are currently under
study and may provide an efficient means of preventing
complications, independent of the ambient glycemic level.
Clin Invest Med 1995; 18 (4): 332-339
Table of contents: CIM vol. 18, no. 4